Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits
| Autor: | Min Wang, Michael E. Goddard, Hans D. Daetwyler, Zhiqian Liu, Sunduimijid Bolormaa, Coralie M. Reich, Christy J. Vander Jagt, Amanda J. Chamberlain, Irene van den Berg, Claire P. Prowse-Wilkins, Iona M. MacLeod, Brett A. Mason, Benjamin J. Hayes, Mogens Sandø Lund, Simone Rochfort, Ruidong Xiang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Multifactorial Inheritance Genome-wide association study Breeding Genome 0302 clinical medicine Databases Genetic 2. Zero hunger Regulation of gene expression 0303 health sciences Multidisciplinary biology Agricultural Sciences Vertebrate 04 agricultural and veterinary sciences animal breeding Biological Sciences Biological Evolution Histone Phenotype PNAS Plus Trait Female Evolution Quantitative Trait Loci Quantitative trait locus quantitative traits 03 medical and health sciences biology.animal Genetic variation evolution Animals Selection Genetic Selection (genetic algorithm) 030304 developmental biology Animal breeding 0402 animal and dairy science Quantitative traits Genetic Variation Heritability 040201 dairy & animal science Gene regulation Gene Expression Regulation Evolutionary biology cattle Expression quantitative trait loci biology.protein Human genome Cattle gene regulation 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Xiang, R, Van Den Berg, I, MacLeod, I M, Hayes, B J, Prowse-Wilkins, C P, Wang, M, Bolormaa, S, Liu, Z, Rochfort, S J, Reich, C M, Mason, B A, Vander Jagt, C J, Daetwyler, H D, Lund, M S, Chamberlain, A J & Goddard, M E 2019, ' Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits ', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 39, pp. 19398-19408 . https://doi.org/10.1073/pnas.1904159116 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance The extent to which variants with genome regulatory and evolutionary roles affect mammalian phenotypes is unclear. We systemically analyzed large datasets covering genomics, transcriptomics, epigenomics, metabolomics, and 34 phenotypes in over 44,000 cattle. This allowed us to provide a framework to rank over 17.7 million sequence variants based on their contribution to gene regulation, evolution, and variation in 34 complex traits. Validated in independent datasets with over 7,500 cattle, our sequence-variant ranking showed consistent performances in genomic prediction of phenotypes. Our study provides methods and an analytical framework to quantify the functional importance of sequence variants. By providing public data of biological priors on genomic markers, our work can make the global selection of animals efficient and accurate. Many genome variants shaping mammalian phenotype are hypothesized to regulate gene transcription and/or to be under selection. However, most of the evidence to support this hypothesis comes from human studies. Systematic evidence for regulatory and evolutionary signals contributing to complex traits in a different mammalian model is needed. Sequence variants associated with gene expression (expression quantitative trait loci [eQTLs]) and concentration of metabolites (metabolic quantitative trait loci [mQTLs]) and under histone-modification marks in several tissues were discovered from multiomics data of over 400 cattle. Variants under selection and evolutionary constraint were identified using genome databases of multiple species. These analyses defined 30 sets of variants, and for each set, we estimated the genetic variance the set explained across 34 complex traits in 11,923 bulls and 32,347 cows with 17,669,372 imputed variants. The per-variant trait heritability of these sets across traits was highly consistent (r > 0.94) between bulls and cows. Based on the per-variant heritability, conserved sites across 100 vertebrate species and mQTLs ranked the highest, followed by eQTLs, young variants, those under histone-modification marks, and selection signatures. From these results, we defined a Functional-And-Evolutionary Trait Heritability (FAETH) score indicating the functionality and predicted heritability of each variant. In additional 7,551 cattle, the high FAETH-ranking variants had significantly increased genetic variances and genomic prediction accuracies in 3 production traits compared to the low FAETH-ranking variants. The FAETH framework combines the information of gene regulation, evolution, and trait heritability to rank variants, and the publicly available FAETH data provide a set of biological priors for cattle genomic selection worldwide. |
| Databáze: | OpenAIRE |
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